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Korean Journal of Obstetrics & Gynecology 2009;52(9):911-919.
Published online September 1, 2009.
Induction of growth inhibition and apoptosis in human endometrial cancer cells by histone deacetylase inhibitors.
Su Yeon Lim, June Kuk Choi, So Jin Shin, Sang Hoon Kwon, Chi Heum Cho, Soon Do Cha, Dong Kum Song
Department of Obstetrics and Gynecology, School of Medicine, Keimyung University, Daegu, Korea. tgjes@hanmail.net
Abstract
OBJECTIVE
Endometrial cancer is the most common malignant tumor of the female genital tract. Its incidence has increased in recent years, making up 13% of female genital cancers. Nevertheless, the search for agents effective in the treatment of either advanced or recurrent endometrial cancer has been disappointing. Histone deacetylase inhibitors (HDACIs) were recently found to be well-tolerated in patients with hematologic and solid malignancies. HDACIs have been shown to inhibit cancer cell proliferation, stimulate apoptosis, and induce cell cycle arrest. Our purpose was to investigate the antiproliferative effects of the HDACIs (sodium butyrate and HDAC-I1) against endometrial cancer cell line (Hec 1A) and normal endometrial cell line (T-HESCs). METHODS: MTS reduction assay was carried out to determine the cell viability. Cell cycle analysis and DNA fragmentation assay was done by fluorescent activated cell sorter analysis. The expression of cell cycle-regulatory and apoptosis-related proteins were evaluated by Western blot. Caspase 3 and 7 activity were measured by immuno-flouorescent staining. RESULTS: Each sodium butyrate and HDAC-I1 induced growth inhibition in a dose and time dependent manner in endometrial cancer cells but did not induce growth inhibition in normal endometrial cells. Treatment with each drugs in endometrial cancer cells increased the percentage of cells in subG1 phase. The expression of p53, p21, p27, FAS, and FAS legand were increased and it was associated with increased p21 and p27 expression in a p53-dependent manner. Activation of caspase-3, 7, 8, 9 and down-regulation of Bcl-2, up-regulation of Bax, with concomitant increase in PARP cleavage, were observed. CONCLUSION: These results demonstrate that sodium butyrate induced growth inhibition and apoptosis in human endometrial cancer cells rising their possibility applicable against human endometrial cancers.
Key Words: Endometrial cancer cell line, Apoptosis, Histone deacetylase inhibitors (HDACIs)


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